Role of tyrosine kinase in serotonin-induced constriction of the basilar artery in vivo.
OBJECTIVE
Serotonin is one of the most potent constrictors of cerebral blood vessels and is implicated in several pathological conditions, including migraine and cerebral ischemia. Recent evidence has suggested that tyrosine kinase is involved in vasocontractile responses. The objective of this study was to test the hypothesis that activation of tyrosine kinase contributes to serotonin-induced constriction of the basilar artery in vivo.


METHODS
Using a cranial window in anesthetized Sprague-Dawley rats, we examined effects of inhibitors of tyrosine kinase and tyrosine phosphatase on constrictor responses of the basilar artery to serotonin in vivo.


RESULTS
Serotonin (10(-8), 10(-7), and 10(-6) mol/L) produced constriction of the basilar artery by 12+/-2%, 27+/-2%, and 37+/-3%, respectively. Genistein (3 x 10(-6) mol/L), an inhibitor of tyrosine kinase, did not affect baseline diameter of the basilar artery but attenuated serotonin-induced vasoconstriction (P<.05 versus control responses). Daidzein, an inactive analogue of genistein, did not affect serotonin-induced constriction of the basilar artery. Tyrphostin 47 (10(-5) mol/L), another inhibitor of tyrosine kinase, also attenuated serotonin-induced vasoconstriction, and tyrphostin 63, an inactive analogue of tyrphostin 47, did not affect the vasoconstriction. Sodium orthovanadate (10(-5) mol/L), an inhibitor of tyrosine phosphatase, enhanced serotonin-induced vasoconstriction. Phorbol 12,13-dibutyrate, a direct activator of protein kinase C, also caused constriction of the basilar artery, which was not affected by genistein or sodium orthovanadate.


CONCLUSIONS
These results suggest that serotonin-induced constriction of the basilar artery is mediated, at least in part, by activation of tyrosine kinase in vivo.
Kitazono
T
T
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. kitazono@intmed2.med.kyushu-u.ac.jp
Ibayashi
S
S
Nagao
T
T
Kagiyama
T
T
Kitayama
J
J
Fujishima
M
M
D000704:Analysis of Variance; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D020032:Tyrphostins; D014638:Vanadates / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D009570:Nitriles; D010636:Phenols; D020032:Tyrphostins; C060152:tyrphostin 47; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D014638:Vanadates; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases